S. Scott Zimmerman

Enantioselective binding of α‐pinene and of some cyclohexanetriol derivatives by cyclodextrin hosts: A molecular modeling study

We have used molecular modeling to investigate the enantioselective separation of the monoterpene α‐pinene on permethylated β‐cyclodextrin and on α‐cyclodextrin and the enantioselective separation of three cyclohexanetriol derivatives on permethylated β‐cyclodextrin. Using the Consistent Valence Force Field (CVFF) from Insight/Discover, we have carried out systematic rigid‐body docking grid searches on each of the optical antipodes of the organic guest molecules interacting with the cyclodextrins, followed by minimizations of the low‐energy docked structures. A statistical mechanical analysis of the minimized energies yields data that agree in four out of five cases with the experimental elution order of enantiomers. The computed energies of the rigid‐body docking before minimizations do not agree with the experimental results, suggesting that a conformational induced fit of the cyclodextrins upon binding of the organic guests may be involved in the mechanism of the chiral recognition.

Molecular Modeling of the Binding of 5‐Substituted 2′‐Deoxyuridine Substrates to Thymidine Kinase of Herpes Simplex Virus Type‐1

In an earlier study, De Winter and Herdewijn (J. Med. Chem. 1996, 37, 4727–4737) studied the binding of various 5‐substituted 2′‐deoxyuridine substrates to thymidine kinase of herpes simplex virus type‐1. They used a computational procedure that achieves good correlation with experimentally determined IC50 values. We applied an alternative procedure to the same deoxyuridine substrates, using only three readily calculated quantities—the binding energy, the molecular surface area, and a flexibility factor. Our simplified method achieves the same degree of correlation with the IC50 values as did the earlier procedure. We then applied this procedure to examine the binding of various 5‐substituted pyrimidine 1,5‐anhydrohexitol substrates to thymidine kinase.

KINETIC AND MOLECULAR MODELING OF NUCLEOSIDE AND NUCLEOTIDE INHIBITION OF MALATE DEHYDROGENASE

ABSTRACT We studied the inhibition of mitochondrial malate dehydrogenase (mMDH) by the nucleotides cAMP, AMP, ADP, ATP. The experimental kinetic studies showed that the nucleotides were competitive inhibitors and that cAMP was probably the most potent inhibitor. To explain these observations, we used molecular modeling to determine the location, orientation, and relative binding energy of the nucleotides to mMDH. The order of the calculated binding energies, from lowest (most favorable) to highest, was cAMP, AMP, ADP, and ATP, which corresponded somewhat to the order of the experimentally determined inhibition constants.

Procedure for selecting starting conformations for energy minimization of nucleosides and nucleotides.

ABSTRACT The purpose of this study was to carry out a thorough search of the conformational space of various adenine-containing nucleotides, applying a previously published searching procedure, known as the representative method. This method, which reduces the number of starting conformations required to explore all the important regions of conformational space, appears to be successful in finding all (or nearly all) the putative low-energy conformations of each molecule.

Conformational energy analysis of peptides using microcomputers: Description of PepCAD™ and analysis of N-formyl-N′-methylalanineamide

Abstract A computer program (called PepCAD™) was developed for performing conformational analysis of peptides on an Apple Macintosh personal computer. The program takes advantage of the mouse-based user interface and graphics of the Macintosh. PepCAD displays peptide molecules, calculates conformational energies, and performs energy minimization on peptides of up to 10 residues. Written in C, PepCAD supports an interactive mode and a batch processing mode, contains about 17,000 lines of code in 11 modules, and utilizes the ECEPP/2 and MINOP equations and parameters for energy calculation and minimization. Conformational energy minimization was done on N-formyl-N′-methylalanineamide. The number of minima and their relative energies were essentially the same as those of N-acetyl-N′-methylalanineamide.

Chapter 4 – Theoretical Methods in the Analysis of Peptide Conformation

Publisher Summary This chapter describes current methods in conformational energy calculations of small peptides. The function of a biologically active peptide is often dictated by its three-dimensional structure. For this reason, many experimental methods have been developed for studying conformations of peptide molecules. Theoretical methods are also valuable in the conformational analysis of peptides. Theory is important for three general reasons: (1) it can provide a model or framework to aid in choosing proper experiments, (2) it can help explain experimental results, and (3) it has the potential of providing information when experiments are difficult or impossible to perform. This chapter presents an introduction to the field of conformational energy calculations of peptides, describes some of the current methodology in conformational energy calculations, and presents some examples of recently published work in the field.

Chemical symbols and special characters on the apple microcomputer

Abstract The utility programs SHAPE TABLE ARTIST, SHAPE TABLE COLLATOR, and SHAPE TABLE VIEWER/RESOLVER have been written to quickly create and utilize shape tables of chemical symbols and special characters for display on the monitor screen of the 48K Apple II Plus microcomputer. Several shape tables—consisting of chemical symbols, mathematical characters, common plotting symbols, Greek letters, special fonts, and standard ASCII alphanumerics in both upper and lower case—have been created. Another program, SHAPE TABLE WRITER, has been written to demonstrate and utilize shape tables in typing chemical equations, mathematical formulas, subscripts and superscripts directly from the keyboard onto the high-resolution screen.